Lack of Gata3 results in conotruncal heart anomalies in mouse.
The transcription factor Gata3 is an important regulator of the development of thymus, the nervous system, ear, kidney, and adrenal glands. This study analyzes the role of Gata3 in the developing heart using a mouse strain containing an nlsLacZ reporter gene fused in frame to the Gata3 gene by homologous recombination. Using in situ hybridization, RT-PCR and Gata3-LacZ histochemistry, Gata3 expression was shown in various cardiac structures up to newborn stage. During looping stages (E9.5-E11.5) Gata3-LacZ activity recapitulated endogenous Gata3 and was abundantly expressed in the endocardial ridges and endothelium of distal outflow tract. Strong reporter gene expression was also noted in the mesenchyme of ventral branchial arches, and in the epithelium. In the atrioventricular canal expression was relatively lower. In the four-chambered heart stages (E13.5-E17.5) the LacZ-staining did not recapitulate the endogenous Gata3 transcript and showed rather lineage tracing of formerly Gata3-expressing cells in the hearts. beta-Galactosidase activity was detected in the cusps of semilunar valves, aorta, pulmonary trunk, innominate and common carotid arteries, and faintly in the atrioventricular valves. Gata3-null embryos die normally between E11 and E12. Pharmacological treatment with sympathomimetic beta-adrenergic receptor agonist lengthens the survival up to E18 when malformations of the heart such as ventricular septal defect (VSD), double-outlet of right ventricle (DORV), anomalies of the aortic arch (AAA) and persistent truncus arteriosus (PTA) were detected. The specified malformations correlate with the normal developmental pattern of Gata3-LacZ expression. The short outflow tract and insufficient rotation of truncus arteriosus during looping stages might be the main reasons underlying these malformations.
Raid
Raivo
R
Department of Developmental Biology, University of Tartu, Tartu, Estonia. raivo.raid@ut.ee
Krinka
Dagni
D
Bakhoff
Lairi
L
Abdelwahid
Eltyeb
E
Jokinen
Eero
E
Kärner
Martin
M
Malva
Merly
M
Meier
Riho
R
Pelliniemi
Lauri J
LJ
Ploom
Merlin
M
Sizarov
Aleksander
A
Pooga
Margus
M
Karis
Alar
A
D000818:Animals; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter / Q000235:genetics; D006330:Heart Defects, Congenital / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D009432:Neural Crest / Q000196:embryology / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics
D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D012333:RNA, Messenger